Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover
Renal osteodystrophy (ROD) is a complex and serious complication of chronic kidney disease (CKD), a major global health problem caused by loss of renal function. Currently, the gold standard to accurately diagnose ROD is based on quantitative histomorphometric analysis of trabecular bone. Although t...
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MDPI AG
2023-01-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/3/598 |
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| author | Yentl Huybrechts Pieter Evenepoel Mathias Haarhaus Etienne Cavalier Geert Dams Wim Van Hul Patrick C. D’Haese Anja Verhulst |
| author_facet | Yentl Huybrechts Pieter Evenepoel Mathias Haarhaus Etienne Cavalier Geert Dams Wim Van Hul Patrick C. D’Haese Anja Verhulst |
| author_sort | Yentl Huybrechts |
| collection | DOAJ |
| description | Renal osteodystrophy (ROD) is a complex and serious complication of chronic kidney disease (CKD), a major global health problem caused by loss of renal function. Currently, the gold standard to accurately diagnose ROD is based on quantitative histomorphometric analysis of trabecular bone. Although this analysis encompasses the evaluation of osteoblast and osteoclast number/activity, tfigurehe interest in osteocytes remains almost nihil. Nevertheless, this cell type is evidenced to perform a key role in bone turnover, particularly through its production of various bone proteins, such as sclerostin. In this study, we aim to investigate, in the context of ROD, to which extent an association exists between bone turnover and the abundance of osteocytes and osteocytic sclerostin expression in both the trabecular and cortical bone compartments. Additionally, the effect of parathyroid hormone (PTH) on bone sclerostin expression was examined in parathyroidectomized rats. Our results indicate that PTH exerts a direct inhibitory function on sclerostin, which in turn negatively affects bone turnover and mineralization. Moreover, this study emphasizes the functional differences between cortical and trabecular bone, as the number of (sclerostin-positive) osteocytes is dependent on the respective bone compartment. Finally, we evaluated the potential of sclerostin as a marker for CKD and found that the diagnostic performance of circulating sclerostin is limited and that changes in skeletal sclerostin expression occur more rapidly and more pronounced. The inclusion of osteocytic sclerostin expression and cortical bone analysis could be relevant when performing bone histomorphometric analysis for diagnostic purposes and to unravel pathological mechanisms of bone disease. |
| first_indexed | 2024-03-11T09:30:43Z |
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| last_indexed | 2024-03-11T09:30:43Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-b344f9a6c8094da4b9ed635386fd590f2023-11-16T17:39:12ZengMDPI AGNutrients2072-66432023-01-0115359810.3390/nu15030598Osteocytic Sclerostin Expression as an Indicator of Altered Bone TurnoverYentl Huybrechts0Pieter Evenepoel1Mathias Haarhaus2Etienne Cavalier3Geert Dams4Wim Van Hul5Patrick C. D’Haese6Anja Verhulst7Laboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, BelgiumLaboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, 3000 Leuven, BelgiumDivision of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, 141 52 Stockholm, SwedenDepartment of Clinical Chemistry, CHU de Liège, Université de Liège, 4000 Liège, BelgiumLaboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, BelgiumCenter of Medical Genetics, University of Antwerp, 2650 Antwerp, BelgiumLaboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, BelgiumLaboratory of Pathophysiology, University of Antwerp, 2610 Antwerp, BelgiumRenal osteodystrophy (ROD) is a complex and serious complication of chronic kidney disease (CKD), a major global health problem caused by loss of renal function. Currently, the gold standard to accurately diagnose ROD is based on quantitative histomorphometric analysis of trabecular bone. Although this analysis encompasses the evaluation of osteoblast and osteoclast number/activity, tfigurehe interest in osteocytes remains almost nihil. Nevertheless, this cell type is evidenced to perform a key role in bone turnover, particularly through its production of various bone proteins, such as sclerostin. In this study, we aim to investigate, in the context of ROD, to which extent an association exists between bone turnover and the abundance of osteocytes and osteocytic sclerostin expression in both the trabecular and cortical bone compartments. Additionally, the effect of parathyroid hormone (PTH) on bone sclerostin expression was examined in parathyroidectomized rats. Our results indicate that PTH exerts a direct inhibitory function on sclerostin, which in turn negatively affects bone turnover and mineralization. Moreover, this study emphasizes the functional differences between cortical and trabecular bone, as the number of (sclerostin-positive) osteocytes is dependent on the respective bone compartment. Finally, we evaluated the potential of sclerostin as a marker for CKD and found that the diagnostic performance of circulating sclerostin is limited and that changes in skeletal sclerostin expression occur more rapidly and more pronounced. The inclusion of osteocytic sclerostin expression and cortical bone analysis could be relevant when performing bone histomorphometric analysis for diagnostic purposes and to unravel pathological mechanisms of bone disease.https://www.mdpi.com/2072-6643/15/3/598chronic kidney disease (CKD)renal osteodystrophy (ROD)parathyroidectomy (PTX)bone turnoverosteocytesclerostin |
| spellingShingle | Yentl Huybrechts Pieter Evenepoel Mathias Haarhaus Etienne Cavalier Geert Dams Wim Van Hul Patrick C. D’Haese Anja Verhulst Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover Nutrients chronic kidney disease (CKD) renal osteodystrophy (ROD) parathyroidectomy (PTX) bone turnover osteocyte sclerostin |
| title | Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover |
| title_full | Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover |
| title_fullStr | Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover |
| title_full_unstemmed | Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover |
| title_short | Osteocytic Sclerostin Expression as an Indicator of Altered Bone Turnover |
| title_sort | osteocytic sclerostin expression as an indicator of altered bone turnover |
| topic | chronic kidney disease (CKD) renal osteodystrophy (ROD) parathyroidectomy (PTX) bone turnover osteocyte sclerostin |
| url | https://www.mdpi.com/2072-6643/15/3/598 |
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